Antidepressant drugs are among the most prescribed pharmaceuticals in the world today. They come in many formulations, and they come with many risks as well. They seem to work for some people, but do the benefits outweigh the risks? And with CBD’s reputation for managing mood and anxiety issues, is it possible that it can go toe-to-toe with Big Pharma against depression? Let’s discuss.

The effectiveness debate
A recent New York Times article goes into detail on some of the complications (and manipulations) around reporting the effectiveness of antidepressant drugs, explaining that “the effectiveness of antidepressants had been overstated, and that the benefit might be limited to far fewer patients than [are] actually using the drugs.”

In fact, the question of whether or not antidepressants really work, and for just how many patients, has been a hotly debated subject for years. While there’s a lot of evidence supporting their effectiveness, some argue that many studies are skewed to align with corporate pharmaceutical sponsors, while others feel that the way that depression and antidepressant statistics are reported is flawed in and of itself.

But one thing seems to be agreed upon almost universally—there has been a steady rise in the use of antidepressant medications across the globe. And surprise, surprise, the United States has a greater percentage of people on antidepressants than any other country. Believe it or not, in 2016 11% of Americans over age 12 was taking an antidepressant.

Those pesky side effects
Another thing that seems to be well understood, effectiveness rates aside, is that antidepressant medications are clearly associated with a myriad of side effects, which can vary from person to person. Some of the more common problems users face include weight gain, insomnia, and sexual dysfunction. There are several different classes of antidepressant drugs, but doctors usually prescribe selective serotonin reuptake inhibitors (SSRIs) first (e.g., Paxil, Prozac, Zoloft, Lexapro) as they seem to be the best-tolerated antidepressants. There are other classes as well, and we will likely get into these in more complexity in the future.

Regardless of the class of antidepressant, to quote the Mayo Clinic: “The Food and Drug Administration (FDA) requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.” Statements like these are not to be taken lightly.

Depression isn’t just chemical—but a lot of it is 
Depression is generally chalked up to a “chemical imbalance,” but it’s important to understand that this is only part of the story, and even this aspect can vary wildly among different people. According to Harvard Health, “Research suggests that depression doesn’t spring from simply having too much or too little of certain brain chemicals. Rather, there are many possible causes of depression, including faulty mood regulation by the brain, genetic vulnerability, stressful life events, medications, and medical problems. It’s believed that several of these forces interact to bring on depression.”

That said, depression has a clear correlation to various regulatory chemicals produced in the brain. Acetylcholine, serotonin, norepinephrine, dopamine, glutamate, and GABA (gamma-aminobutyric acid) are the neurotransmitters that scientists seem to think are most closely linked to depression. Here’s Harvard again: “Brain cells usually produce levels of neurotransmitters that keep senses, learning, movements, and moods perking along. But in some people who are severely depressed or manic, the complex systems that accomplish this go awry. For example, receptors may be oversensitive or insensitive to a specific neurotransmitter, causing their response to its release to be excessive or inadequate.”

We’ve already mentioned the SSRIs (which affect serotonin levels) above. Those and pretty much all other classes of pharmaceutical antidepressants work to affect one or more of the aforementioned neurotransmitters. Why is this so fascinating? Because CBD can interact with many of the same receptors in the brain and nervous system that antidepressants do. This means that CBD can aid in the signaling and production of chemicals that can help reduce depression symptoms, just like many antidepressant drugs—but without the “black box warnings.”

Evidence suggests CBD can accomplish what popular depression meds do
One of the most noteworthy recent (2016) studies on CBD for depression comes from Spain, where three-month-old mice were given an operation called an olfactory bulbectomy, which is a standard procedure that has been used to model depression for the purpose of clinical study. These “OBX” mice, as they are called, exhibited the expected signs of depression, along with changes in serotonin and glutamate production. The mice were given both chemical and behavioral tests as the researchers monitored their condition while they administered doses of CBD. The findings were overwhelmingly positive—CBD seemed to have beneficial effects on both acute and chronic models of depression. The really interesting thing is that CBD is seen as being able to target and affect serotonin and glutamate production much like SSRIs and other antidepressants, but with a much quicker response.

To quote the study’s conclusion: “CBD is a multitarget drug that can modulate a variety of systems implicated in mood control and therefore result in a great value from a clinical point of view. This work evidences that CBD could represent a novel drug for treating depressive disorders in a very fast manner, acting via the enhancement of serotonergic and glutamatergic transmission…. The fast onset of antidepressant action of CBD and the simultaneous anxiolytic effect would solve some of the main limitations of the current antidepressant therapies.”

Another study from 2011 makes a direct correlation between the functioning of the endocannabinoid system (ECS) and potential root causes of—and treatments for—depression. To quote the abstract: “Clinical populations diagnosed with depression are found to have reduced levels of circulating endocannabinoids and preclinical models of depression reveal a deficit in central endocannabinoid signaling. Moreover, facilitation of endocannabinoid signaling is sufficient to produce all of the behavioral and biochemical effects of conventional antidepressant treatments [boldface = ours].”

There are numerous other studies on how CBD can affect various neurochemical processes to help regulate anxiety and mood disorders, and how the health of the ECS also plays a role in these processes. (See also “How CBD Works” and “Clinical Endocannabinoid Deficiency” if you’d like to take a deeper dive.)

Back to Harvard: “While researchers know more now than ever before about how the brain regulates mood, their understanding of the biology of depression is far from complete.” Perhaps the discovery of the ECS and its role in mood disorders can help to shed more light on the biological mysteries of depression. For the time being, though, what’s truly exciting is that CBD may represent a viable alternative to the most popularly prescribed antidepressants, interacting with the same receptors to elicit similar neurochemical effects. If CBD is capable of correcting the balance of neurotransmitters in the brain that help control depression, maybe it’s time to rethink those high-risk/low-reward prescriptions? We hope that in due time, further research cracks the case on how cannabis medicine and ECS health can help to offset the overprescribing of antidepressant drugs. Are you curious about trying CBD? Read “What to Look for in a CBD Product” next.


RESOURCES:
https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0087089/
http://www.businessinsider.com/countries-largest-antidepressant-drug-users-2016-2
https://www.nytimes.com/2018/03/12/upshot/do-antidepressants-work.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltext
https://www.ncbi.nlm.nih.gov/pubmed/24923339
https://www.health.harvard.edu/mind-and-mood/what-causes-depression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181155/
https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046273
https://www.uttbio.com/cbd-generates-rapid-antidepressant-effects-via-advanced-cortical-signaling/
https://repositorio.unican.es/xmlui/bitstream/handle/10902/11358/CannabidiolEnhancementSerotonergic.pdf?sequence=1
https://www.ncbi.nlm.nih.gov/pubmed/21111017

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